Synthesis of 2-Aminopyrroles by Sequential MCR/[4+1] Cycloaddition

Abstract

Reported is an efficient two-step synthesis of unsymmetrical polysubstituted 2-aminopyrroles from α,β-unsatured aldehydes. By combining a [4+1] cycloaddition with the oxidative three-component Strecker reaction developed previously by Zhu for the synthesis of α-imino­nitriles 2 (P. Fontaine, A. Chiaroni, G. Masson, J. Zhu Org. Lett. 2008, 10, 1509), diversely substituted pyrroles 3 have been readily prepared. Indeed, after optimization of the [4+1] cycloaddition, a considerable number of aromatic and aliphatic isocyanides was studied, affording 2-amino-5-­cyanopyrroles in good to excellent yield. However, in the presence of α-isocyanoacetamide 5, a Michael addition reaction occurred to afford the oxazole 6.